Estrogen in Luteal Phase Support: Effects on IVF-ICSI Antagonist Protocol Pregnancy Results

Abstract

Aim: This study aimed to investigate the effect of luteal phase support (LPS) with estradiol in addition to progesterone on pregnancy outcomes in patients who underwent ovulation induction with GnRH antagonist protocol in in vitro fertilization- intracytoplasmic sperm injection (IVF-ICSI).
 Materials and Methods: This retrospective study was carried out at reproductive medicine center of Necmettin Erbakan University Meram Medical Faculty. The study enrolled 128 patients undergoing ICSI on an antagonist protocol for controlled ovarian hyperstimulation. Study group administered 7.8 mg transdermal estradiol (E2) daily in addition to progesterone for LPS (n=64). Control group administered only progesterone for LPS (n=64). All women received 200 mg progesterone 3x1 intravaginal daily and 50 mg progesterone intramuscular injection per two days for LPS. Blood samples were drawn 12 days after embryo transfer for β-hCG. If the result is negative, treatment was discontinued, if positive, estradiol was discontinued and progesterone support was continued until the 10th week of gestation. Pregnancy outcomes were the main endpoint.
 Results: There was no difference between groups in terms of biochemical pregnancy, clinical pregnancy, abortus and ongoing pregnancy rates.
 Conclusion: In our study, the use of estrogen for luteal phase support in GnRH antagonist protocol did not show any difference on pregnancy outcomes.

Estrogen Supplementation to Progesterone as Luteal Phase Support in Patients Undergoing in Vitro Fertilization

“…Regarding ovarian stimulation outcomes, the number of embryos transferred on day five of oocyte retrieval differed significantly between the groups, with single embryo transfer in 31.1% of the progesterone-only group and 68% in the estradiol + progesterone group, while two embryos were transferred in 66.9% of the progesterone-only group and 31% in the estradiol + progesterone group. However, there was no statistically significant difference in the number of frozen embryos between the two groups, in agreement with a study conducted at 2022 [4] while in another study, (1) they found no significant difference in the number of embryo transfers between the progesterone and estrogen groups [1,4].…”

“…Endometrial thickness, assessed by ultrasound examination, is commonly used as a marker of endometrial receptivity (p>0.05). However, this finding contrasts with studies conducted at 2020 and 2022 which reported a significant difference in endometrial thickness between estradiol and control groups [1,4] , differences in endometrial thickness between estradiol+progesterone and progesterone-only groups, potentially may impact pregnancy outcomes [4].…”

“…The primary outcome, "Clinical pregnancy," was defined as the presence of gestational sacs with a fetal heartbeat on ultrasound 14 days after a positive pregnancy test [9]. The secondary outcomes included "Chemical pregnancy," which referred to a positive serum βhCG result without the detection of an intrauterine or extrauterine gestational sac on vaginal ultrasound [4], and "early miscarriage," defined as pregnancy loss occurring spontaneously before 12 weeks of gestation with an initially positive pregnancy test and ultrasound evidence of a gestational sac with a fetal pole [10]. No statistically significant difference between the two groups regarding the cause of infertility.…”

“…Assess the occurrence of pregnancy by serum quantitative B-HCG 14 days after embryo transfer, women considered pregnant if had a quantitative B-HCG test (A value above 50 IU/mL) were considered a positive pregnancy (chemical pregnancy) and considered clinically pregnant with +ve fetal heart rate by ultrasound, which examined by transvaginal ultrasound 4 weeks after embryo transfer or 2 weeks from +ve B-HCG. It was considered a positive pregnancy (chemical pregnancy) with positive serum βhCG level with no intrauterine or extrauterine gestational sac by ultrasound and considered clinically pregnant with a +ve fetal heart rate which, examined by transvaginal ultrasound 4 weeks after embryo transfer or 2 weeks from +ve B-HCG [4]. Women who were pregnant followed up for the first trimester.…”

“…In IVF cycles, Serum estradiol levels can be decreased during progesterone-only treatment in the mid-luteal phase, potentially affecting pregnancy rates and causing luteal vaginal bleeding. Adding estradiol to progesterone in LPS can enhance the probability of pregnancy [4].…”